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Vorinostat in Treating Patients With Locally Advanced, Recurrent, or Metastatic Adenoid Cystic Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01175980
First received: August 4, 2010
Last updated: November 25, 2014
Last verified: November 2014
  Purpose

This phase II trial studies how well vorinostat works in treating patients with adenoid cystic carcinoma that has come back or that has spread from where it started to nearby tissue or lymph nodes. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Recurrent Oral Cavity Adenoid Cystic Carcinoma
Recurrent Salivary Gland Carcinoma
Salivary Gland Adenoid Cystic Carcinoma
Stage III Major Salivary Gland Carcinoma
Stage III Oral Cavity Adenoid Cystic Carcinoma
Stage IVA Major Salivary Gland Carcinoma
Stage IVA Oral Cavity Adenoid Cystic Carcinoma
Stage IVB Major Salivary Gland Carcinoma
Stage IVB Oral Cavity Adenoid Cystic Carcinoma
Stage IVC Major Salivary Gland Carcinoma
Stage IVC Oral Cavity Adenoid Cystic Carcinoma
Tongue Carcinoma
Drug: Vorinostat
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Suberoylanilide Hydroxamic Acid (SAHA) in Subjects With Locally Advanced, Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response according to RECIST 1.1 criteria [ Time Frame: Up to 180 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 180 days ] [ Designated as safety issue: Yes ]
    Toxicity will be tabulated via frequency distributions, and also dichotomized to report the proportion (and percentage) of patients experiencing a specified level (e.g., grade 3-4) of toxicity. Analysis of these proportions (i.e., rates) will include both point and 90% confidence interval (CI) estimates, with the CI estimates calculated via Wilson's method.

  • TTR [ Time Frame: From the start of the treatment until the RECIST measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded, assessed up to 180 days ] [ Designated as safety issue: No ]
    TTR will be summarized descriptively, reporting N, median, mean, standard deviation, standard error (SE), minimum, maximum, and 90% CI for the mean calculated from the SE and asymptotic normal distribution theory.

  • RD [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 180 days ] [ Designated as safety issue: No ]
    Distribution will be estimated using standard survival analysis techniques, and the Kaplan-Meier (K-M) method. From the K-M life tables, both point and 90% CI estimates of various statistics of interest can be calculated (e.g., median, 6-month event-free rate, 12-month event-free rate, etc.). Statistical graphs of each K-M curve (with 90% CI lines) will be generated for visual display.

  • PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 180 days ] [ Designated as safety issue: No ]
    Distribution will be estimated using standard survival analysis techniques, and the K-M method. From the K-M life tables, both point and 90% CI estimates of various statistics of interest can be calculated (e.g., median, 6-month event-free rate, 12-month event-free rate, etc.). Statistical graphs of each K-M curve (with 90% CI lines) will be generated for visual display.

  • OS [ Time Frame: From the start of treatment until death from any cause, assessed up to 180 days ] [ Designated as safety issue: No ]
    Distribution will be estimated using standard survival analysis techniques, and the K-M method. From the K-M life tables, both point and 90% CI estimates of various statistics of interest can be calculated (e.g., median, 6-month event-free rate, 12-month event-free rate, etc.). Statistical graphs of each K-M curve (with 90% CI lines) will be generated for visual display.


Other Outcome Measures:
  • Metabolic response by PET/CT scan [ Time Frame: Up to 56 days ] [ Designated as safety issue: No ]
    Will assess the association between a metabolic response by PET/CT after one course of chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria. Will also assess the association between a metabolic response by PET/CT after the first and second chemotherapy courses and PFS.

  • Flow sort diploid populations of tumor cells from FFPE tissue blocks [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Reported as descriptive results.

  • Flow sort aneuploid populations of tumor cells from FFPE tissue [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Reported as descriptive results.

  • Flow sort tetraploid populations of tumor cells from FFPE tissue [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Reported as descriptive results.

  • Genomic profile of each cell population using oligonucleotide CGH arrays [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Reported as descriptive results.

  • Whole exome profile of the sorted tumor population and matching germ line sample [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Reported as descriptive results. The combined CGH array and exome data will be mined to identify genes and pathways that are targeted by select somatic events in each of the patient subsets.

  • SDD [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Reported as descriptive results.

  • Expression level of HR23B [ Time Frame: Up to day 180 ] [ Designated as safety issue: No ]
    Exact logistic modeling investigation would yield a point and 90% CI estimate of the odds ratio for response.


Estimated Enrollment: 29
Study Start Date: August 2010
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat)
Patients receive vorinostat PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy by means of response rate (based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) of vorinostat in the treatment of patients with locally advanced, recurrent or metastatic adenoid cystic carcinoma (ACC).

SECONDARY OBJECTIVES:

I. To characterize the safety and tolerability of vorinostat in this patient population.

II. To assess the time to tumor response (TTR). III. To assess the response duration (RD). IV. To evaluate progression free survival (PFS). V. To assess overall survival (OS).

TERTIARY OBJECTIVES:

I. To assess the association between a metabolic response by positron emission tomography (PET)/computed tomography (CT) after one cycle of chemotherapy and subsequent best tumor response according to standard anatomic response evaluation criteria (RECIST).

II. To assess the association between a metabolic response by PET/CT after the first and second chemotherapy cycle and PFS.

III. To assess flow sort diploid, aneuploid, and tetraploid populations of tumor cells from formalin fixed, paraffin-embedded (FFPE) tissue blocks from patients who benefited from suberoylanilide hydroxamic acid (SAHA) therapy and from patients who did not demonstrate a durable benefit.

IV. Profile the genomes of each cell population using oligonucleotide comparative genomic hybridization (CGH) arrays.

V. Perform whole exome analysis of the sorted tumor population and matching germ line sample for each of the patients selected.

VI. To assess stable disease duration (SDD). VII. To assess the association between response to vorinostat treatment and RAD23 homolog B (HR23B) on tumor paraffin blocks.

OUTLINE:

Patients receive vorinostat orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 180 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed locally advanced, recurrent or metastatic adenoid cystic carcinoma
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm by chest x-ray, as >= 10 mm with CT scan, or >= 10 mm with calipers by clinical exam; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters)
  • Patients must have locally advanced and/or recurrent and/or metastatic disease not amenable to potentially curative surgery or radiotherapy; any prior number of chemotherapy regimens is allowed; a minimum of at least 4 weeks since prior chemotherapy or radiation therapy should have elapsed, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C
  • Life expectancy of greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits (WNL)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
  • Creatinine within normal institutional limits OR
  • Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of vorinostat will be determined following review of their case by the principal investigator
  • No other diagnosis of malignancy unless non-melanoma skin cancer, carcinoma in situ of the cervix, or a malignancy diagnosed >= 5 years previously and currently with no evidence of disease; however - if the patient has had a previously diagnosed stage I/II malignancy of another type, consideration for recruitment may be made by the Cancer Therapy Evaluation Program (CTEP) senior investigator after discussion with local principal investigator (PI) and patient's physician
  • Confirmed availability of tumor tissue (either fresh or from paraffin block) from the primary tumor or metastatic site to be available to use on correlative studies
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • If the patient's tumor can be easily accessed, a pre-treatment biopsy will be mandatory

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; more than 21 days from major surgery should have elapsed before the first dose of the study drug
  • Patients may not be receiving any other investigational agents or have received vorinostat in the past; patients should not have taken valproic acid for at least 4 weeks prior to enrollment
  • Inability to take oral medications on a continuous basis
  • Patients with active brain metastases should be excluded from this clinical trial; patients with previous brain metastases will be eligible if condition is treated and stable for >= 1 month
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat
  • Patient is unable or unwilling to abide by the study protocol and to cooperate fully with the investigator or designee
  • Patient on current therapy with enzyme-inducing anticonvulsants
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01175980

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
City of Hope Medical Group Inc
Pasadena, California, United States, 91105
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Maryland
National Cancer Institute
Rockville, Maryland, United States, 20850
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Veterans Administration
Cleveland, Ohio, United States, 44106
Lake University Ireland Cancer Center
Mentor, Ohio, United States, 44060
Ireland Cancer Center at Firelands Regional Medical Center
Sandusky, Ohio, United States, 44870
Canada, Ontario
Ontario Cancer Institute at Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Investigators
Principal Investigator: Patricia LoRusso Wayne State University/Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01175980     History of Changes
Other Study ID Numbers: NCI-2012-02981, NCI-2012-02981, 2009-165, 8474, U01CA062487, U01CA062505, U01CA062502, U01CA132123, P30CA022453
Study First Received: August 4, 2010
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Adenoid Cystic
Salivary Gland Neoplasms
Adenocarcinoma
Head and Neck Neoplasms
Mouth Diseases
Mouth Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Salivary Gland Diseases
Stomatognathic Diseases
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014